Elevated insulin levels and insulin resistance in Pima Indian diabetics and nondiabetics suggest that cellular changes external to the pancreas may be important in the pathogenesis of obesity and diabetes mellitus. The aim of this project was to study several aspects of insulin function in cultured cells obtained from normal and diabetic Pima Indians, in order to determine if diabetes mellitus is expressed in genetic differences in insulin action at the cellular level. Fibroblast cultures have been established from normal and diabetic Pima Indians. Cellular metabolism and transport function were studied in the presence and absence of insulin, in order to define cell insulin action in this system. A system was also developed to measure glucose transport in endothelial cell cultures derived from umbilical veins, and insulin was observed to stimulate transport in growing cells but not in confluent monolayers. No differences were observed in any of the measurable parameters of insulin action in cells derived from diabetics, suggesting that there may not be intrinsic differences in cellular response to insulin in type 2 diabetics. Since there were no observed differences in this system relevant to the changes which occur in vivo in diabetics.